Mechanism for ionic environment formation and organelle trafficking by proton-pumping V-ATPase

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07939
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Iwate Medical University
• Principal Investigator: Nakanishi Mayumi 岩手医科大学, 薬学部, 教授 (20270506)
• Co-Investigator(Renkei-kenkyūsha): GOTO NAOMI 岩手医科大学, 薬学部, 助教 (80403971) ; SEKIYA MIZUKI 岩手医科大学, 薬学部, 助教 (70509033) ; WADA GE-HONG (SUN GE-HONG) 同志社女子大学, 薬学部, 教授 (00314427) ; WADA YOH 大阪大学, 産業科学研究所, 准教授 (50212329)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: プロトンポンプ / 酸性環境 / オルガネラ輸送 / 破骨細胞 / ATPase

Outline of Final Research Achievements

Osteoclast secretory lysosomes move toward the plasma membrane and release their enzymes required for bone resorption. We have shown that a3 isoform of proton-pumping V-ATPase has an essential role in outward trafficking of secretory lysosomes. The a3 is lysosome-specific isoform of the a subunit that forms the proton pathway in V-ATPase. Using a3-knockout mice, we found that a3 is indispensable for recruitment of Rab7, a small GTPase involved in lysosome trafficking. We also found that a3 specifically interacts with inactivated-form of Rab7. These results suggest that a3 recruits Rab7 to secretory lysosomes through their direct interaction. Secretory lysosomes are involved in various cell type-specific functions, such as secretion of pore-forming protein from cytotoxic T cells and metastasis of cancer cells. Thus, our findings will provide a new insight into these functions, and promote development of novel treatments for related diseases.

Free Research Field

生化学、細胞生物学